1-62210002-C-T

Variant names:

• chr1-62210002-C-T
• rs141196718
• NM_019079.5:c.1228C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019079.5(L1TD1):​c.1228C>T​(p.Pro410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 1,468,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000074 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: L1TD1 NM_019079.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.24
• Publications: 4 publications found

Genes affected

L1TD1 (HGNC:25595): (LINE1 type transposase domain containing 1) Predicted to enable single-stranded RNA binding activity. Predicted to be involved in transposition, RNA-mediated. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028768599).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L1TD1	NM_019079.5	MANE Select	c.1228C>T	p.Pro410Ser	missense	Exon 4 of 4	NP_061952.3
	L1TD1	NM_001164835.2		c.1228C>T	p.Pro410Ser	missense	Exon 5 of 5	NP_001158307.1	Q5T7N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L1TD1	ENST00000498273.2	TSL:1 MANE Select	c.1228C>T	p.Pro410Ser	missense	Exon 4 of 4	ENSP00000419901.1	Q5T7N2
	L1TD1	ENST00000928897.1		c.1228C>T	p.Pro410Ser	missense	Exon 5 of 5	ENSP00000598956.1
	L1TD1	ENST00000928898.1		c.1228C>T	p.Pro410Ser	missense	Exon 4 of 4	ENSP00000598957.1

Frequencies

GnomAD3 genomes AF: 0.00000736 AC: 1 AN: 135884 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000163

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000806 AC: 2 AN: 247988 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1332172 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 663502

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28778

American (AMR) AF: 0.00 AC: 0 AN: 42014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24220

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5170

European-Non Finnish (NFE) AF: 9.91e-7 AC: 1 AN: 1008706

Other (OTH) AF: 0.00 AC: 0 AN: 54832

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000736 AC: 1 AN: 135884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 66468

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 35384

American (AMR) AF: 0.00 AC: 0 AN: 14028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3230

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000163 AC: 1 AN: 61360

Other (OTH) AF: 0.00 AC: 0 AN: 1856

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.033
DANN	Benign	0.63
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.0010
Sift	Benign	0.98	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.27		Gain of phosphorylation at P410 (P = 1e-04)
MVP		0.067
MPC		0.042
ClinPred		0.017	T
GERP RS		-2.0
Varity_R		0.021
gMVP		0.013
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141196718; hg19: chr1-62675674;